A combination of irinotecan/cisplatinum and irinotecan/temozolomide or tumor-targeting Salmonella typhimurium A1-R arrest doxorubicin- and temozolomide-resistant myxofibrosarcoma in a PDOX mouse model

Myxofibrosarcoma (MFS) is the most common sarcomas in elderly patients and is either chemo-resistant or recurs with metastasis after chemotherapy. This recalcitrant cancer in need of improved treatment. We have established a patient-derived orthotopic xenograft (PDOX) of MFS. The MFS PDOX model was...

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Published in:Biochemical and biophysical research communications 2018-11, Vol.505 (3), p.733-739
Main Authors: Kiyuna, Tasuku, Tome, Yasunori, Murakami, Takashi, Miyake, Kentaro, Igarashi, Kentaro, Kawaguchi, Kei, Oshiro, Hiromichi, Higuchi, Takashi, Miyake, Masuyo, Sugisawa, Norihiko, Zhang, Zhiying, Razmjooei, Sahar, Wangsiricharoen, Sintawat, Chmielowski, Bartosz, Nelson, Scott D., Russell, Tara A., Dry, Sarah M., Li, Yunfeng, Eckardt, Mark A., Singh, Arun S., Chawla, Sant, Kanaya, Fuminori, Eilber, Fritz C., Singh, Shree Ram, Zhao, Ming, Hoffman, Robert M.
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
CHEMOTHERAPY
DOXORUBICIN
Irinotecan
METASTASES
MICE
Myxofibrosarcoma
Patient-derived orthotopic xenograft
S. typhimurium A1-R
SALMONELLA TYPHIMURIUM
SARCOMAS
Temozolomide
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Summary:Myxofibrosarcoma (MFS) is the most common sarcomas in elderly patients and is either chemo-resistant or recurs with metastasis after chemotherapy. This recalcitrant cancer in need of improved treatment. We have established a patient-derived orthotopic xenograft (PDOX) of MFS. The MFS PDOX model was established in the biceps femoris of nude mice and randomized into 7 groups of 7 mice each: control; doxorubicin (DOX); pazopanib (PAZ); temozolomide (TEM); Irinotecan (IRN); IRN combined with TEM; IRN combined with cisplatinum (CDDP) and Salmonella typhimurium A1-R (S. typhimurium A1-R). Treatment was evaluated by relative tumor volume and relative body weight. The MFS PDOX models were DOX, PAZ, and TEM resistant. IRN combined with TEM and IRN combined with CDDP were most effective on the MFS PDOX. S. typhimurium A1-R arrested the MFS PDOX tumor. There was no significant body weight loss in any group. The present study suggests that the combination of IRN with either TEM or CDDP, and S. typhimurium have clinical potential for MFS. •Myxofibrosarcoma (MFS) is the most common sarcomas in elderly patients.•Established patient-derived orthotopic xenograft (PDOX) of Myxofibrosarcoma.•The MFS PDOX models were DOX, PAZ, and TEM resistant.•Combination of IRN with either TEM or CDDP, and S. typhimurium have clinical potential for myxofibrosarcoma.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2018.09.106